Uptake of 3H-dopamine in megakaryocytes and blood platelets measured by quantitative electron-microscope autoradiography

Daimon, Tateo; David, Heinz

doi:10.1007/bf00508426

Cited by 7 publications

(1 citation statement)

References 13 publications

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“…In fact, the delayed appearance of thrombocytopenia after [1311]MIBG therapy and its progressive severity in patients previously treated with radio-01-chemotherapy, suggests an earlier cause, most likely by damage to the progenitor mcgakaryocytes. It has been demonstrated that megakaryocytcs are as potent as platelets in concentrating various monoamines (Schick and Weinstein, 1981;Daimon and David, 1986), and contain a radiosensitive nucleus (Tanum, 1984).…”

Section: Discussionmentioning

confidence: 99%

Uptake of the neuron‐blocking agent meta‐iodobenzylguanidine and serotonin by human platelets and neuro‐adrenergic tumour cells

Rutgers

Tytgat

Verwijs-Janssen

et al. 1993

Intl Journal of Cancer

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The adrenomedulla-imaging agent meta-iodobenzylguanidine (MIBG) is concentrated by various tumours of neuroectodermal origin. Radio-iodinated [131I]MIBG is therefore increasingly used for diagnosis and therapy of these disorders. To study the cause of thrombocytopenia associated with [131I]MIBG therapy, we investigated the uptake of MIBG in human platelets in comparison with that of serotonin. Specific imipramine-sensitive uptake of [131I]MIBG was much slower than of [3H]serotonin, but after prolonged incubation high and serotonin-equivalent uptake levels were observed. Accumulation of MIBG saturated at 10- to 100-fold higher concentration than serotonin, and the affinity for uptake and intracellular storage in platelets was much higher for serotonin than for MIBG. Conversely, serotonin was not detectably concentrated by neuroadrenergic Uptake-I in SK-N-SH neuroblastoma and PC12 pheochromocytoma cells. Fluvoxamine inhibited the uptake of norepinephrine and MIBG in PC12 cells, similarly to that of serotonin in platelets. However, the drug was 100-fold more effective in inhibiting platelet transport of MIBG than of serotonin. The results indicate that MIBG uptake in platelets is not mediated by a neuro-adrenergic Uptake-I, but probably proceeds via the serotonin transport system. MIBG concentration by platelets was at least as efficient as in neuro-adrenergic tumour cells and has therefore (radio)biological potential for injuring these cells or precursor megakaryocytes. Platelet uptake of MIBG could be selectively blocked by fluvoxamine in concentrations which minimally affected its accumulation in neuro-adrenergic target cells.

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Section: Discussionmentioning

confidence: 99%

Uptake of the neuron‐blocking agent meta‐iodobenzylguanidine and serotonin by human platelets and neuro‐adrenergic tumour cells

Rutgers

Tytgat

Verwijs-Janssen

et al. 1993

Intl Journal of Cancer

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Location of sites of dopamine storage in megakaryocytes by autoradiography

1990

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We have used quantitative electron microscope autoradiography to study the subcellular sites of 3H-dopamine uptake in mouse megakaryocytes after a single intraperitoneal injection. Autoradiographic grains were found to be associated almost exclusively with the vesicles of precursors of monoamine-storage organelles. The labeling intensity (radioactivity) of the demarcation membrane system which is continuous with the plasmalemma was also significantly greater than would be expected. On the other hand, radioactivity associated with the remaining sites in the cytoplasm was not significantly different from that expected of a random distribution. In order to compare 3H-dopamine uptake during cell maturation, light microscope autoradiographic studies were also done. Immature megakaryocytes were labeled slightly, but the number of silver grains increased significantly in maturing cells. Mature megakaryocytes were 2.7 times more radioactive than the maturing cells. Our results suggest that the megakaryocytes were able to accumulate dopamine from the early stages of cell maturation and to store dopamine in precursors of monoamine-storage organelles.

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Platelets as a model for neurones?

et al. 1988

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The multiple biochemical and pharmacological similarities existing between blood platelets and 5-hydroxytryptamine (5-HT)-containing neurones of the CNS point to the platelets as a reliable model for the biochemical characterization of 5-HT releasers and uptake blockers which interfere with the storage and the active carrier mechanism of 5-HT in the neurones, respectively. In addition, the affinity displayed by dopamine and by dopaminergic neurotoxin MPP+ for the platelet 5-HT transport and storage indicates also some similarities between platelets and the dopaminergic system of the CNS. Since human platelets contain almost exclusively monoamine oxidase type B (MAO-B), they can be used as a source for the purification and characterization of this human enzyme. Human platelets thus offer an excellent peripheral model to indirectly assess the degree and duration of MAO-B inhibition occurring in the CNS. To date, knowledge of the many biochemical mechanisms underlying platelet physiology is still fragmentary. In fact, the functional role of binding sites located on the platelet cytoplasmic membrane, i.e. their coupling to a specific transmembrane signalling mechanism, is still in need of a precise biochemical and physiological characterization.

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Uptake of 3H-dopamine in megakaryocytes and blood platelets measured by quantitative electron-microscope autoradiography

Cited by 7 publications

References 13 publications

Uptake of the neuron‐blocking agent meta‐iodobenzylguanidine and serotonin by human platelets and neuro‐adrenergic tumour cells

Uptake of the neuron‐blocking agent meta‐iodobenzylguanidine and serotonin by human platelets and neuro‐adrenergic tumour cells

Location of sites of dopamine storage in megakaryocytes by autoradiography

Platelets as a model for neurones?

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